한빛사논문
- 조회2,781
Abstract
, Keykavous Parang , and Gongqin Sun *
Departments of *Cell and Molecular Biology and Biomedical Sciences, University of Rhode Island, Kingston, RI 02881
Edited by R. L. Erikson, Harvard University, Cambridge, MA, and approved October 15, 2003 (received for review July 17, 2003)
Abstract:
Protein tyrosine kinases (PTK) are key enzymes of mammalian signal transduction. For the fidelity of signal transduction, each PTK phosphorylates only one or a few proteins on specific Tyr residues. Substrate specificity is thought to be mediated by PTK-substrate docking interactions and recognition of the phosphorylation site sequence by the kinase active site. However, a substrate-docking site has not been determined on any PTK. C-terminal Src kinase (Csk) is a PTK that specifically phosphorylates Src family kinases on a C-terminal Tyr. In this study, by sequence alignment and site-specific mutagenesis, we located a substrate-docking site on Csk. Mutations in the docking site disabled Csk to phosphorylate, regulate, and complex with Src but only moderately affected its general kinase activity. A peptide mimicking the docking site potently inhibited (IC50 = 21 ？) Csk phosphorylation of Src but only moderately inhibited (IC50 = 422 ？) its general kinase activity. Determination of the substrate-docking site provides the structural basis of substrate specificity in Csk and a model for understanding substrate specificity in other PTKs.
To whom correspondence should be addressed at: Department of Cell and Molecular Biology, University of Rhode Island, 117 Morrill Science Building, 45 Lower College Road, Kingston, RI 02881.
논문정보
- Research article
- 2003년 12월 (BRIC 등록일 )
- 국외 연구진
댓글 작성 로그인
팝업 닫기관련 링크
